Abstract
ObjectivesTo examine whether educational attainment and intelligence have causal effects on risk of Alzheimer’s disease (AD), independently of each other.DesignTwo-sample univariable and multivariable Mendelian randomization (MR) to estimate the causal effects of education on intelligence and vice versa, and the total and independent causal effects of both education and intelligence on AD risk.Participants17 008 AD cases and 37 154 controls from the International Genomics of Alzheimer’s Project (IGAP) consortium.Main outcome measureOdds ratio (OR) of AD per standardized deviation increase in years of schooling (SD = 3.6 years) and intelligence (SD = 15 points on intelligence test).ResultsThere was strong evidence of a causal, bidirectional relationship between intelligence and educational attainment, with the magnitude of effect being similar in both directions [OR for intelligence on education = 0.51 SD units, 95% confidence interval (CI): 0.49, 0.54; OR for education on intelligence = 0.57 SD units, 95% CI: 0.48, 0.66]. Similar overall effects were observed for both educational attainment and intelligence on AD risk in the univariable MR analysis; with each SD increase in years of schooling and intelligence, odds of AD were, on average, 37% (95% CI: 23–49%) and 35% (95% CI: 25–43%) lower, respectively. There was little evidence from the multivariable MR analysis that educational attainment affected AD risk once intelligence was taken into account (OR = 1.15, 95% CI: 0.68–1.93), but intelligence affected AD risk independently of educational attainment to a similar magnitude observed in the univariate analysis (OR = 0.69, 95% CI: 0.44–0.88).ConclusionsThere is robust evidence for an independent, causal effect of intelligence in lowering AD risk. The causal effect of educational attainment on AD risk is likely to be mediated by intelligence.
Highlights
Alzheimer’s disease (AD) is the leading cause of death in England and Wales.[1]
If the principal direction of causality is such that greater educational attainment increases intelligence, interventions designed to prolong the duration of education may reduce AD risk, either directly or indirectly through subsequently increasing intelligence
The magnitude of the effect was over two-fold greater for educational attainment on intelligence compared with intelligence on educational attainment
Summary
Alzheimer’s disease (AD) is the leading cause of death in England and Wales.[1]. Existing treatments are currently unable to reverse or delay progression of the disease. The degree to which education affects intelligence, vs intelligence being largely fixed in early life and acting as a determinant of educational attainment, has been debated for decades[6,7,8,9,10] and studies have provided evidence of an effect in both directions.[8,11] If the principal direction of causality is intelligence to educational attainment, intelligence would induce confounding bias in the association between educational attainment and AD In this case, interventions aiming to increase educational attainment (e.g. raising the school leaving age to increase years of schooling) are unlikely to affect AD risk, but alternative prevention strategies such as cognitive training may prove effective. If the principal direction of causality is such that greater educational attainment increases intelligence (i.e. intelligence lies on the causal pathway from educational attainment to AD risk), interventions designed to prolong the duration of education may reduce AD risk, either directly or indirectly through subsequently increasing intelligence
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